胃癌患者血清miR-518a-3p、miR-376c-3p、sPD-L1、sCTLA-4表达水平与临床病理特征及预后的关系研究OA

Objective To investigate the serum expression levels of microRNA(miR)-518a-3p,miR-376c-3p,soluble cytotoxic T lymphocyte-associated protein 4(sCTLA-4),and soluble programmed death-ligand 1(sPD-L1)in gastric cancer patients,and to analyze their associations with clinical pathological characteristics and prognosis.Methods This retrospective study included 179 gastric cancer patients treated at the First People's Hospital of Chuzhou from September 2019 to June 2022 as the gastric cancer group,and 158 healthy individuals undergoing routine physical examinations during the same period as the control group.Serum levels of miR-518a-3p,miR-376c-3p,sPD-L1,and sCTLA-4 were measured and compared between the groups.Associa-tion with clinicopathological characteristics of gastric cancer patients were analyzed.The predictive values of each marker for gastric cancer occurrence and prognosis were evaluated using the area under the receiver operating characteristic curve(AUC).Three-year overall survival(OS)rates of gastric cancer patients were compared between different expression level groups using Kaplan-Meier survival curves.Results Serum levels of miR-518a-3p(1.98±0.45)and miR-376c-3p(0.99±0.34)in the case group were significantly lower than those in the control group(4.12±1.23,3.67±1.23,respectively),while serum sPD-L1(4.67±1.77)and sCTLA-4(10.21±2.34)levels were significantly higher than those in the control group(1.51±0.45,4.79±1.55,respectively)(t=21.694～27.971,all P<0.05).Deseased patients had significantly higher serum sPD-L1(6.02±1.47)and sCTLA-4(11.67±2.89)levels and significantly lower miR-518a-3p(1.89±0.56)and miR-376c-3p(1.07±0.31)levels compared with surviving group(3.78±1.64,6.56±1.59,3.68±1.29,and 3.45±1.23,respectively)(t=9.571～17.251,all P<0.05).ROC analysis indicated that the combined use of the four markers for diagnosing gastric cancer yielded an AUC of 0.992,significantly higher than that of each marker alone(Z=3.759～6.103,all P<0.001).The combined pre-dictive AUC for prognosis was 0.997,also significantly higher than individual markers(Z=2.176～5.534,all P<0.05).All four markers were significantly associated with TNM stage,tumor diameter,lymph node metastasis,tumor differentiation grade,and distant metastasis(miR-514b-3p:t=10.490～14.274;miR-376c-3p:t=13.021～16.528;sPD-L1:t=6.143～8.204;sCTLA-4:t=8.626～13.183,all P<0.05).Kaplan-Meier survival curves revealed significantly lower OS in patients with low miR-518a-3p and miR-376c-3p expression compared to high expression groups(Log-rank χ2=82.138,158.448,both P<0.05),while patients with high expression of sPD-L1 or sCTLA-4 had significantly poorer OS than those with low expression(Log-rank χ2=42.328,139.243,both P<0.05).Conclusions Low serum expression of miR-518a-3p and miR-376c-3p,along with high expression of sPD-L1 and sCTLA-4,are significantly associated with clinicopathological characteristics and poor prognosis in gastric cancer patients.Combined assessment of these four markers holds significant clinical value for prognostic evaluation of gastric cancer.